Homocystinuria
Overview
A deficiency of cystathionine beta-synthase (CBS) results in the inability to degrade homocystine to cystathionine, resulting in increased levels of homocysteine and methionine. A variant that represents a minority of cases is responsive to vitamin B6 (pyridoxine), but this type may be missed by newborn screening. Elevated homocysteine impairs the function of several proteins (including fibrillin) interfering with the formation of disulfide bonds and impairs endothelial function, leading to thrombosis.Incidence
About 1:200,000 - 1:300,000 live births, as high as 1:65,000 in Ireland [Homocystinuria - Information for Professionals (STAR-G) Homocystinuria (GeneReviews)Prenatal Testing
DNA testing by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified. Enzyme assay possible by amniocentesis.Clinical Characteristics
With treatment normal IQ is possible and reduction of thromboembolic events may decrease the incidence of other sequelae, such as ectopia lentis, seizures, and psychiatric problems. Without treatment, symptoms vary widely and may present at different ages, ranging from lens dislocation, poor vision, developmental delays, marfanoid habitus, and acute thromboembolism.Initial symptoms in infants and toddlers may include:
- Developmental delay
- Emotional and behavior problems
- Thromboembolism
- Ectopia lentis (dislocation of the ocular lens) or severe myopia (nearsightedness)
- Marfanoid habitus: tall/ thin build; long fingers, arms, and legs
- Genu valgum, pes cavus
- Osteoporosis
- Malar flush
- Decreased hair, skin, iris pigmentation
- Seizures
- Vascular disease and stroke
- Psychiatric abnormalities
- Mental retardation
Follow-up Testing after Positive Screen
Quantitative plasma amino acid analysis, total plasma homocysteine.Primary Care Management
Upon Notification of the + Screen
- Contact the family and evaluate the infant for poor feeding or other problems.
- Urgent treatment is not likely to be needed in the newborn period, but patients should be referred immediately (see the ACT Sheet for Homocystinuria (ACMG) (
347 KB) for additional information).
- To confirm the diagnosis, work with the following service(s): see all Newborn Screening Programs services providers (3) in our database.
- For evaluation and ongoing collaborative management, consult the following service(s): see all Pediatric Genetics services providers (5) in our database.
If the Diagnosis is Confirmed
- Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Homocystinuria - Information for Parents (STAR-G)).
- Assist in implementation and maintenance of a diet low in methionine and proteins; baby aspirin is also recommended starting in late teenager years.
- Provision of vitamin B6, betaine, vitamin B12, and methylfolate may be indicated.
- Regular blood and urine tests to monitor amino acid levels and diet may be indicated.
- For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.
Specialty Care Collaboration
Initial consultation with the following service(s): see all Pediatric Genetics services providers (5) in our database and ongoing collaboration if the child is affected. A dietician may work with the family to devise an optimal approach to dietary management. Genetic counseling for the family.Resources
Information & Support
For Professionals
Homocystinuria (GeneReviews)
Excellent review that includes a clinical description and information about differential diagnoses, management, genetic counseling,
and molecular genetics; sponsored by the National Center for Biotechnology Information (NCBI).
Homocystinuria Resources (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; National Library
of Medicine and the Genetic Alliance.
Homocystinuria (OMIM)
Extensive literature review organized by description, clinical features, genetics, diagnosis, differential diagnosis, management,
nomenclature, history, and animal models; Online Mendelian Inheritance in Man.
Utah Newborn Screening Program (UDOH)
Provides information about the program, related legislation, training for practices, and newborn conditions; Utah Department
of Health.
For Parents and Patients
Homocystinuria - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received
an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.
Homocystinuria (Genetics Home Reference)
Excellent, detailed review for patients and families affected by homocystinuria; a service of the U.S. National Library of
Medicine.
Tools
ACT Sheet for Homocystinuria (ACMG) ( 347 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical
Genetics.
Services in Utah
Newborn Screening Programs
See all Newborn Screening Programs services providers (3) in our database.
For other services related to this condition, browse our Services categories or search our database.
Helpful Articles
PubMed search for homocystinuria and neonatal screening, last 5 years.
Mudd SH.
Hypermethioninemias of genetic and non-genetic origin: A review.
Am J Med Genet C Semin Med Genet.
2011;157(1):3-32.
PubMed abstract
Discusses briefly the genetic and non-genetic conditions that sometimes lead to abnormally elevated methionine. Focuses on
recent developments and differential diagnosis of hypermethioninemia.